There is a need for a process for preparing alkyl-L-alanyl-L -proline derivatives of the general formula I which results in an optically pure compound having an SSS configuration, and which is free of other stereoisomers, and in which the use of noxious phosgene, diphosgene or triphosgene is avoided.
According to known processes (U.S. Pat. No. 4,374,829), the synthesis of alkyl-L-alanyl-L-proline derivatives of the general formula I is carried out by a reduction of a Schiff's base (A), which is prepared by condensation of L-alanyl-L-proline (B) and ethyl-4-phenyl-2-oxobutanoate (C). In the reduction of the Schiff's base various catalysts are used and thus L-alanyl-L-proline derivatives having differing SSS/RSS isomer ratios are obtained. ##STR2##
To avoid the formation of undesired RSS isomer, EP 0215 335 A discloses a method of preparing alkyl-L-alanyl-L-proline derivatives of the general formula I by reacting N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxy anhydride of the formula III and L-proline (E) in the presence of bases in aqueous media (acetone-water). ##STR3##